Takimoto Yukinobu, Dixit Vivek, Arthur Marika, Gitnick Gary
University of California, Los Angeles, Department of Medicine, Division of Digestive Diseases, UCLA School of Medicine, Center for the Health Sciences, Los Angeles, CA 90095-7019, USA.
Cell Transplant. 2003;12(4):413-21. doi: 10.3727/000000003108746966.
In experimental and clinical settings hepatocyte transplantation has provided limited benefit to patients with chronic liver disease because the transplanted hepatocytes were short-lived and were merely maintained for a brief period within the body. Except for whole-liver transplantation, creation of de novo liver tissue is necessary to treat this condition on a long-term basis. The aim of this study was to facilitate the formation of new tissue by actual self-regeneration, rather than by compensatory hypertrophy, or scar formation, with our collagen-polypropylene composite scaffold. Collagen-polypropylene composite scaffolds, not containing hepatocytes, were implanted into the median liver lobe and the dynamics of new liver tissue formation was analyzed immunohistochemically over a 6-month period. Control scaffolds consisted of polypropylene scaffolds without collagen matrix. The control scaffold implants remained hollow throughout the study period and became encapsulated with a hard connective tissue capsule 1 week after implantation. In contrast, the collagen-polypropylene composite scaffold was filled with regenerating tissue structures 3 weeks after implantation. At this time, the predominant cell type within the scaffold was sesmin-positive stellate cells. A week earlier, oval cells were identified using monoclonal antibody staining (OV-6). Subsequently, these cells differentiated into alpha-fetoprotein-positive immature hepatocytes. After 6 months, mature liver tissue, juxtaposed with bile ducts and blood vessels, was seen within the polypropylene scaffolds. We report the first evidence of de novo formation of liver tissue within a polypropylene scaffold, following implantation in the liver. This scaffold may play a role in treating chronic liver diseases requiring organ replacement therapy.
在实验和临床环境中，肝细胞移植对慢性肝病患者的益处有限，因为移植的肝细胞寿命较短，仅在体内短暂维持。除了全肝移植外，长期治疗这种疾病需要重新创建肝脏组织。本研究的目的是利用我们的胶原蛋白 - 聚丙烯复合支架，通过实际的自我再生促进新组织的形成，而不是通过代偿性肥大或瘢痕形成。将不含肝细胞的胶原蛋白 - 聚丙烯复合支架植入肝中叶，并在6个月的时间内通过免疫组织化学分析新肝组织形成的动态过程。对照支架由不含胶原基质的聚丙烯支架组成。在整个研究期间，对照支架植入物一直保持中空，并在植入后1周被坚硬的结缔组织囊包裹。相比之下，胶原蛋白 - 聚丙烯复合支架在植入后3周充满了再生组织结构。此时，支架内的主要细胞类型是结蛋白阳性的星状细胞。一周前，通过单克隆抗体染色（OV - 6）鉴定出卵圆细胞。随后，这些细胞分化为甲胎蛋白阳性的未成熟肝细胞。6个月后，在聚丙烯支架内可见与胆管和血管并列的成熟肝组织。我们报告了首次在肝内植入聚丙烯支架后肝脏组织从头形成的证据。这种支架可能在治疗需要器官替代疗法的慢性肝病中发挥作用。
